The aim of the proposed research program is the development of effective immunotherapy for human cancer utilizing two immunoreactive extracts of lymphoid tissues - "Immune" RNA and transfer factor. Work performed in our laboratories over the past several years has established that immunoreactive preparations of lymphoid ribonucleic acid can mediate immune responses to tumor specific transplantation antigens in a variety of animal model systems. Recently, limited clinical trials of transfer factor immunotherapy in cancer patients have been reported and a few encouraging responses noted. Since we have shown in animal models that xenogeneic sources of "Immune" RNA are active in these systems, we will undertake the immunotherapy of human cancer with preparations of xenogeneic "Immune" RNA. It will first be necessary to show, in vitro, that xenogeneic "Immune" RNA, prepared from the lymphoid organs of animals immunized to human tumors, will transform normal human lymphoid cells to specific anti-tumor immunoreactive status. Studies now in progress are aimed at selecting the most suitable animal species to use as a source of anti- tumor "Immune" RNA. "Immune" RNA is being prepared from the lymphoid organs of guinea pigs, sheep and monkeys. When the optimal animal species has been selected, experimental immunotherapy will then be undertaken by two modalities: 1) the direct administration of "Immune" RNA in solutions containing an RNAase inhibitor, 2) the infusion of autologous lymphocytes following incubation, in vitro, with "Immune" RNA. Transfer factor will be isolated from the peripheral blood leukocytes of: 1) patients exhibiting positive skin tests to preparations of human tumor antigens, 2) patients who have successfully completed immunotherapy by other modalities and who have exhibited good responses, and 3) patients immunized with killed allogeneic tumor cells of the tumor type to be treated. Transfer factor will then be administered to patients weekly by subcutaneous injection.